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Clostridioides Difficile: a Public Health Threat in Plain Sight Clostridioides Difficile (Pronounced: Klos-TRID-E-OY-Dees Dif-Uh-SEEL) – Or C

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Clostridioides Difficile: a Public Health Threat in Plain Sight Clostridioides Difficile (Pronounced: Klos-TRID-E-OY-Dees Dif-Uh-SEEL) – Or C Clostridioides difficile: A Public Health Threat in Plain Sight Clostridioides difficile (pronounced: klos-TRID-e-OY-dees dif-uh-SEEL) – or C. difficile – is a bacterium (germ) that can cause a serious and potentially life-threatening infection associated with symptoms from diarrhea to severe intestinal infections.1,2 Recognizing the CDC defining C. difficile infection as an urgent public The Founding Committee of the health threat, a group of experts representing a cross-section of C. difficile Awareness Initiative includes: healthcare professionals and patient organizations impacted by this infectious disease launched the C. difficile Awareness Initiative. Working James C. Appleby, BSPharm, together, and with support from Pfizer Inc., this multidisciplinary panel MPH, Chief Executive Officer, of experts represents infectious disease specialists, physicians, The Gerontological Society of and nurses as well as representatives of patient support groups and America. www.geron.org (aging professional organizations. They share a common mission: to build and community representative) expand public awareness of and education around C. difficile. The focus is to reach a broad spectrum of people who are potentially at risk Erik R. Dubberke, MD, MSPH, Professor of Medicine, of contracting this infection. Washington University School of Medicine. (C. difficile/ The C. difficile Awareness Initiative’s goal is helping both the healthcare infectious disease expert) community and the general public understand three critical points surrounding this public health issue: Millicent Gorham, PhD (Hon), MBA, FAAN, Executive Director, National Black Nurses 1 2 3 Association. www.nbna.org (nursing representative) C. difficile bacteria C. difficile infection CDI can be a can be anywhere (CDI) is unpredictable debilitating disease Christian John Lillis, and persistent and can occur Executive Director, in anyone, Peggy Lillis Foundation. particularly adults www.peggyfoundation.org (C. difficile patient representative) This Call-to-Action represents the group’s broad array of experience Artie L. Shelton, MD, Colonel, with and understanding of the current disease state. It provides a closer USA (Ret), Director of the examination of the issues to establish a more widespread understanding Vietnam Veterans of America’s of C. difficile and raise awareness of the potential risks for and impact of Veterans Health Council. the infection. The goal is to galvanize relevant experts and organizations www.vva.org/what-we-do/ to work collectively toward solutions for combatting this potentially outreach-programs/veterans- serious infectious disease. health-council/ (veteran representative) Jennifer Moïsi, PhD, Senior Director, Medical and Scientific Affairs and Global Medical Lead, Bacterial Pipeline Vaccines, Pfizer Inc., www.Pfizer.com (industry representative) 1 A closer look at antibiotic-associated diarrhea,10 a public health threat and may be responsible for an USA C. difficile is a Gram-positive estimated 15 to 25 percent of all 462,100 CDI cases yearly anaerobic germ that, when outside antibiotic-associated diarrhea in the body, forms spores that are hospitalized patients in the United inactive and can lie dormant for States (US) with the risk increasing 7,8,9 with the severity of disease and the EUROPE months or sometimes years. 10 When ingested, however, the spores age of the patient. Once CDI has 172,000 have the ability to germinate into occurred, the use of antibiotics to CDI cases yearly the pathogenic vegetative (active) treat CDI further compromises the form and “bloom” in the intestines intestinal microbiota integrity and may prevent the recovery of the of people with an imbalance of 13 gut bacteria, such as those taking gut microbiome. What’s in a name? antibiotics, the elderly, and those In with compromised immune Clostridioides vs. Clostridium systems.7 In healthy intestines with 2017: First identified in 1935 and named Bacillus a normal microbiome, the checks difficilis, the bacterium was originally believed 224,000 20,500 3 and balances of neighboring, & to be part of normal gut microbiota. The hospitalizations deaths associated “difficilis” part of the name comes from the beneficial bacteria help prevent this with the infection germination and proliferation difficulty scientists had in culturing this germ. Four decades later, in the 1970s, researchers of C. difficile spores.7 12,800 reclassified it as Clostridium difficile given that, like other members of the genus Clostridium, “From my experience, more people were directly related to C. difficile due to antibiotic-resistant infection C. difficile also is anaerobic, Gram positive, in the US are familiar with Ebola than and spore-forming.4,5 Most recently in 2016, C. difficile, even though the risk of getting Despite more than a decade of taxonomists determined that C. difficile had been misclassified as Clostridium, based Ebola is significantly lower. We need to intervention and notable decreases work together and as collaboratively as on improved genetic testing with 16S rRNA in hospital associated infections, gene sequencing.6 The analysis determined possible to continue educating people and including a 12 percent decrease in that the organism is actually located within healthcare workers.” C. difficile infections between 2017 the Peptostreptococcaceae family of Gram- and 2018, the burden of C. difficile positive bacteria and proposed reclassifying – Christian John Lillis, on both affected people and health it as “Peptoclostridium difficile.” 6 Noting that Peggy Lillis Foundation systems remains high.14,15 According changing the name of this microorganism from C. difficile/C. diff to P. difficile/P. diff could The disease-causing effects from to the most recent US Centers for Disease Control and Prevention create confusion and impact patient care, C. difficile are mainly due to two several microbiologists proposed renaming it exotoxins – toxin A and toxin B – (CDC) surveillance data, the burden of C. difficile infection in the US Clostridioides difficile so that the germ could though not all C. difficile germs retain the commonly-used C. difficile name.6 7 remains high and represents a are able to produce toxins. These 16 exotoxins cause the C. difficile critical unmet medical need. infection by damaging the cells of A CDC study – published in April 2020 – estimated the national the colon and causing inflammation, “C. difficile can be anywhere. Spores have been burden of CDI to be 462,100 resulting in signs and symptoms cultured from dust, from livestock, and from that can range from mild to severe cases (95 percent CI, 428,600 to 495,600) in 2017. This equates food purchased at grocery stores. Even our pets diarrhea, as well as cramping, can be colonized with C. difficile. We think of fever, nausea, and, in severe cases, to an estimated incidence of an infectious disease like C. difficile as being intestinal inflammation, toxic 144 cases per 100,000 persons. megacolon (enlargement of the When accounting for the type of associated with hospitals and people who are colon), and even death.10,11,12 The laboratory assay used to determine already sick, but the spores have been found use of antibiotic therapy, advanced the diagnoses, the adjusted even in the homes of otherwise healthy people.” age, and having significant number of cases may be lower but 17 – Dr. Erik R. Dubberke, health problems resulting in still substantial. (see Estimating Washington University School hospitalization, are primary risk the Burden of CDI on page 3) In of Medicine factors for the development of addition, nearly 70,000 people CDI.10,12 In healthcare and community had at least one recurrence of settings, these infections can cause CDI (incidence ~22 per 100,000 2 Estimating the Burden of CDI17 persons), there were 224,000 CDI- and an increased risk of disability 19 According to a recent CDC study by Alice Guh, et al related hospitalizations (incidence (morbidity) and death (mortality). (NEJM 2020), the overall incidence of CDI reported ~70 per 100,000 persons) and between 2011 and 2017 has declined, driven primarily 20,500 CDI-associated in hospital The CDC classified C. difficile by a decrease in the incidence of healthcare- deaths (incidence ~6 per 100,000 at “Hazard Level—Urgent,” when associated cases. Using data from the CDC’s persons) in 2017 in the US.17 Of the it published its first report in 2013 Emerging Infections Program (EIP) – CDI-associated deaths, at least on germs that pose high antibiotic a population-based CDI surveillance in 10 states 12,800 deaths are directly related to resistance threats.2 C. difficile among a population of 12 million people – Guh and C. difficile due to antibiotic-resistant remained at this threat level in colleagues estimated that the number of laboratory- infection.2 Outside the US, an the CDC’s follow-up report in 2019, confirmed CDI cases in persons >two years of age in estimated 172,000 CDI cases occur signifying the difficult nature the US declined from 476,400 (155 per 100,000) in 2011 18 2 to 462,100 (144 per 100,000) in 2017. annually in Europe. of this infectious germ. According to the CDC, “Hazard Level—Urgent” CDI cases were confirmed by EIP surveillance Each year, more than $7 billion threats have the potential to laboratories using NAAT (nucleic acid is spent in the US and European become widespread and therefore amplification test) either alone or in combination Union (EU) in C. difficile-related require urgent attention to identify with an enzyme immunoassay for toxins. NAAT costs.18,19,20 The disease also and prevent transmission of is a highly-sensitive laboratory test that detects contributes to longer hospital infection.2 Globally, the World Health the gene that encodes the C. difficile toxin. Given stays,18,21 decreased productivity,18,22 Organization (WHO) has recognized that NAAT does not detect the actual presence reduced quality of life,19,22,23 C. difficile as a priority pathogen.24 of the C. difficile toxin, there are concerns that increasing reliance on this test has led to an overdiagnosis of the infection.
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